Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol.
OBJECTIVE
This study was designed to investigate whether the in vivo metabolism of tramadol was influenced by CYP2D6 polymorphism.


METHODS
The extent of tramadol O- and N-demethylation was calculated by determining the amounts of tramadol and O- and N-desmethyltramadol in 24 h urine after ingestion of a test dose of tramadol. The O- and N-demethylation rates were calculated by dividing the 24-h urinary excretion amount of tramadol by that of O- and N-desmethyltramadol. Volunteers were phenotyped for CYP2D6 polymorphism using sparteine as an in vivo probe.


CONCLUSIONS
High correlation was found between tramadol-O-demethylation and sparteine oxidation in 71 extensive metabolizers of sparteine (rs = 0.544). The mean metabolic ratio of tramadol O-demethylation was significantly higher in poor metabolizers of sparteine than in extensive metabolizers (4.4 vs 0.8). These in vivo results confirm that tramadol O-demethylation is carried out to a large extent by the polymorphic CYP2D6.
Paar
W D
WD
Department of General Internal Medicine, University of Bonn, Venusberg, Germany.
Poche
S
S
Gerloff
J
J
Dengler
H J
HJ
D000328:Adult; D000701:Analgesics, Opioid / Q000378:metabolism*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000502:physiology; D003640:Dealkylation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013034:Sparteine / Q000378:metabolism; D014147:Tramadol / Q000378:metabolism*
D000701:Analgesics, Opioid; D013034:Sparteine; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6